Crowding, then self-assembly
Add a little surfactant to water and the molecules go straight to the surface, lining up with tails pointing into the air. Add more, and the surface fills up. Once the surface is saturated and there is nowhere left to escape the water, the extra molecules do something elegant: they huddle together in the bulk liquid, tails tucked inward away from water and heads facing out, forming a tiny sphere called a micelle. The water-hating tails are now hidden in an oily core; the water-loving heads form a friendly outer shell.
The concentration at which micelles first start to form is sharp and reproducible. It is called the critical micelle concentration, or CMC. Below the CMC you have only free, single (monomeric) surfactant molecules; above it, every extra molecule you add goes into new micelles, while the concentration of free monomers stays almost constant.
A hidden oily compartment
Here is why micelles matter so much in pharmacy. The core of a micelle is essentially a droplet of oil-like environment, suspended in water. A drug that barely dissolves in water but happily dissolves in oil can slip into that core and ride along in solution. This is solubilisation: using micelles to carry far more poorly water-soluble drug than the water could ever hold on its own. It is one of the standard tools — alongside cosolvency and complexation — for rescuing a drug with low solubility.
Where the drug sits depends on its character. Very oily molecules dissolve deep in the hydrocarbon core; more polar ones nestle among the head groups near the surface; intermediate ones sit in between. The amount a system can carry rises only after you pass the CMC — below it there are no micelles to do the carrying, so adding surfactant does little.
Worked example: solubilisation capacity A drug's intrinsic water solubility = 0.05 mg/mL Surfactant CMC = 2 mg/mL Measured 'solubilisation capacity' above CMC: 0.20 mg drug per mg of micellised surfactant If we use 50 mg/mL of surfactant: micellised surfactant = 50 - 2 (CMC) = 48 mg/mL drug carried in micelles = 48 x 0.20 = 9.6 mg/mL + free in water = 0.05 mg/mL -------------------------------------------- total apparent solubility ~= 9.65 mg/mL A ~190-fold gain over plain water — but note ONLY the surfactant ABOVE the CMC does useful work.
What shifts the CMC
- Longer hydrocarbon tail → lower CMC. A bigger oily tail is more eager to escape water, so micelles form at a lower concentration.
- Added salt → lower CMC (for ionics). Salt screens the repulsion between charged heads, letting them pack into micelles more easily.
- Nonionics have far lower CMCs than ionics — often a hundred times lower — because there is no head-group repulsion to overcome.